title: Amniotic fluid stem cells with low γ-interferon response showed behavioral improvement in Parkinsonism rat model.
abstract: Amniotic fluid stem cells (AFSCs) are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA) of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs) following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain's circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.
authors.affiliation: Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Tsung-Yen
authors.initials: TY
authors.lastname: Ho
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Wu
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Tzyy-Wen
authors.initials: TW
authors.lastname: Chiou
authors.forename: Ming-Song
authors.initials: MS
authors.lastname: Tsai
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D052160:Benzothiazoles; D017931:DNA Primers / Q000235:genetics; D003959:Diamines; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000276:immunology / Q000378:metabolism*; D009930:Organic Chemicals; D016627:Oxidopamine / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D011804:Quinolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D017931:DNA Primers; D003959:Diamines; D006680:HLA Antigens; D009930:Organic Chemicals; D011804:Quinolines; D014157:Transcription Factors; C098022:SYBR Green I; D007371:Interferon-gamma; D016627:Oxidopamine